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1. 发明申请

US20210381997A1 ELECTRIC FIELD-ASSISTED JUNCTIONS FOR SEQUENCING 有权
公开(公告)号：US20210381997A1
公开(公告)日：2021-12-09
申请号：US17286366
申请日：2019-06-19
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER , Zsolt MAJZIK , Flint MITCHELL , Juraj TOPOLANCIK
IPC分类号： G01N27/327 , C12Q1/6869
摘要： Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific 5 nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. An electric field may be applied to move the nucleic acid molecule and the moiety close to the tunneling junction so that a current may travel through the moiety. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through 10 the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

2. 发明申请

US20190390267A1 TUNNELING JUNCTIONS FOR SEQUENCING 审中-公开
公开(公告)号：US20190390267A1
公开(公告)日：2019-12-26
申请号：US16445635
申请日：2019-06-19
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER , Juraj TOPOLANCIK , Hannes KUCHELMEISTER , Frank BERGMANN , Dieter HEINDL , Nikolaus Klaus-Peter STEINGELE
IPC分类号： C12Q1/6869 , C12Q1/6876 , G01N15/10
摘要： Molecules may be analyzed (e.g., sequencing of nucleic acid molecules) by tunneling recognition at a tunneling junction. Embodiments of the present invention may allow detecting individual nucleotides and the sequencing of a nucleic acid molecule using a tunneling junction. By labeling a specific nucleotide with a moiety, tunneling junctions may generate a signal with a suitable signal-to-noise ratio. The tunneling recognition uses a tunneling current that is mostly through the moiety rather than mostly through the nucleotide or a portion of the molecule of interest. Because a single nucleotide can be detected with a signal with a suitable signal-to-noise ratio resulting from the tunneling current passing through the moiety, embodiments of the present invention may allow for fast detection of nucleotides using a tunneling current.

3. 发明申请

US20200239951A1 METHODS AND SYSTEMS FOR NUCLEIC ACID SEQUENCING BY TUNNELING RECOGNITION 审中-公开
公开(公告)号：US20200239951A1
公开(公告)日：2020-07-30
申请号：US16839875
申请日：2020-04-03
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER
IPC分类号： C12Q1/6869 , G01N27/327 , G01N33/487
摘要： Nucleic acid molecule analysis systems are described. The system may include a nucleic acid molecule attached to a particle with a characteristic dimension. The system may also include an aperture defined by a first electrode, a first insulator, and a second electrode. The aperture may have a characteristic dimension less than the characteristic dimension of the particle. The system may further include a first power supply in electrical communication with the first electrode and the second electrode. In addition, the system may include a second power supply configured to apply an electric field through the aperture. In some embodiments, the aperture may be defined by a first insulator. A portion of the first electrode may extend into the aperture. A portion of the second electrode may extend into the aperture.

4. 发明申请

US20190112652A1 METHODS AND SYSTEMS FOR NUCLEIC ACID SEQUENCING BY TUNNELING RECOGNITION 审中-公开
公开(公告)号：US20190112652A1
公开(公告)日：2019-04-18
申请号：US16218938
申请日：2018-12-13
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER
IPC分类号： C12Q1/6869 , G01N33/487 , G01N27/327
摘要： Embodiments may include a method of analyzing a nucleic acid molecule. The method may include attaching the nucleic acid molecule to a protein. The protein may be attached to a particle with a first diameter. The method may also include applying an electric field to move a first portion of the nucleic acid molecule into an aperture. The aperture may be defined by a first electrode, an insulator, and a second electrode. The aperture may have a second diameter less than the first diameter. The method may further include contacting the first portion of the nucleic acid molecule to both the first electrode and the second electrode. The method may include applying a voltage across the first electrode and the second electrode. The current through the electrodes and the portion of the nucleic acid molecule may be measured, and a nucleotide of the nucleic acid molecule may be identified.

5. 发明申请

US20220404347A1 METHODS FOR DETECTING AN ANALYTE USING STRUCTURE SWITCHING BINDING AGENTS 有权
公开(公告)号：US20220404347A1
公开(公告)日：2022-12-22
申请号：US17350822
申请日：2021-06-17
申请人： Roche Diagnostics Operations, Inc. , Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER , Dieter HEINDL , Hannes KUCHELMEISTER , Nikolaus-Peter STENGELE
IPC分类号： G01N33/543 , C12N15/115 , C12N15/10
摘要： The present invention relates to diagnostic test and technology. In particular, it relates to a method for determining an analyte suspected to be present in a sample comprising contacting said sample with at least one sensor element comprising at least one binding agent which is capable of specifically binding to the analyte and which comprises at least one magnetic label; and in functional proximity thereto a magnetic tunnel junction generating a signal which is altered upon binding of the analyte to the binding agent for a time and under conditions which allow for specific binding of the analyte suspected to be present in the sample to the at least one binding agent, measuring an altered signal generated by the magnetic tunnel junction upon analyte binding to the at least one binding agent comprising the at least one magnetic label, and determining the analyte based on the altered signal which is generated by the magnetic tunnel junction. The present invention further relates to a device for determining an analyte suspected to be present in a sample and for using such a device. Moreover, the present invention furthermore relates to an aptamer which is capable of specifically binding to an analyte and which comprises at least one magnetic label and a method for identifying such an aptamer. Finally, the invention relates to a kit for determining an analyte suspected to be present in a sample.

6. 发明申请

US20220193670A1 NUCLEIC ACID SEQUENCING BY SYNTHESIS USING MAGNETIC SENSOR ARRAYS 有权
公开(公告)号：US20220193670A1
公开(公告)日：2022-06-23
申请号：US17602319
申请日：2020-04-08
申请人： Roche Sequencing Solutions, Inc. , Western Digital Technologies, Inc.
发明人： Yann ASTIER , Patrick BRAGANCA , Juraj TOPOLANCIK
IPC分类号： B01L3/00 , G01N27/08 , G01N27/74 , G01N33/58
摘要： Disclosed herein are apparatuses for nucleic acid sequencing, and methods of making and using such apparatuses. In some embodiments, the apparatus comprises a magnetic sensor array comprising a plurality of magnetic sensors, each of the plurality of magnetic sensors coupled to at least one address line, and a fluid chamber adjacent to the magnetic sensor array, the fluid chamber having a proximal wall adjacent to the magnetic sensor array. In some embodiments, a method of sequencing nucleic acid using the apparatus comprises (a) coupling a plurality of molecules of a nucleic acid polymerase to the proximal wall of the fluid chamber; (b) in one or more rounds of addition, adding, to the fluid chamber, (i) a nucleic acid template comprising a primer binding site and an extendable primer, and (ii) a first magnetically-labeled nucleotide precursor comprising a first cleavable magnetic label, a second magnetically-labeled nucleotide comprising a second cleavable magnetic label, a third magnetically-labeled nucleotide comprising a third cleavable magnetic label, and a fourth magnetically-labeled nucleotide comprising a fourth cleavable magnetic label; and (c) sequencing the nucleic acid template, wherein sequencing the nucleic acid template comprises, using the at least one address line, detecting a characteristic of at least a portion of the magnetic sensors in the magnetic sensor array, wherein the characteristic indicates which of the first, second, third, or fourth magnetically-labeled nucleotide precursors has been incorporated into the extendable primer. In some embodiments, a method of sequencing nucleic acid using the apparatus comprises (a) binding a nucleic acid strand to the proximal wall; (b) in one or more rounds of addition, adding, to the fluid chamber, (i) an extendable primer, and (ii) a plurality of molecules of a nucleic acid polymerase; (c) adding, to the fluid chamber, a first magnetically-labeled nucleotide precursor comprising a first cleavable magnetic label; and (d) sequencing the nucleic acid template, wherein sequencing the nucleic acid template comprises, using the at least one address line, detecting a characteristic of at least a first portion of the magnetic sensors in the magnetic sensor array, wherein the characteristic indicates that the first magnetically-labeled nucleotide precursor has bound to at least one molecule of the plurality of molecules of the nucleic acid polymerase or has been incorporated into the extendable primer. In some embodiments, a method of manufacturing a nucleic acid sequencing device having at least one fluid chamber configured to contain fluid comprises fabricating a first addressing line on a substrate, fabricating a plurality of magnetic sensors, each magnetic sensor having a bottom portion and a top portion, wherein each bottom portion is coupled to the first addressing line, depositing a dielectric material between the magnetic sensors, fabricating a plurality of additional addressing lines, each of the plurality of additional addressing lines coupled to the top portion of a respective magnetic sensor of the plurality of magnetic sensors, and removing a portion of the dielectric material adjacent to the plurality of magnetic sensors to create the at least one fluid chamber.

7. 发明申请

US20200282392A1 DEVICES FOR SAMPLE ANALYSIS USING EPITACHOPHORESIS 审中-公开
公开(公告)号：US20200282392A1
公开(公告)日：2020-09-10
申请号：US16763782
申请日：2018-11-13
申请人： ROCHE SEQUENCING SOLUTIONS, INC.
发明人： Yann ASTIER , Jan BERKA , Ulrich SCHLECHT , Frantisek FORET , Vladimira DATINSKA , Ivona VORACOVA
IPC分类号： B01L3/00 , G01N27/447
摘要： The present disclosure generally relates to devices for effecting epitachophoresis. Epitachophoresis may be used to effect sample analysis, such as by selective separation, detection, extraction, and/or pre-concentration of target analytes such as, for example, DNA, RNA, and/or other biological molecules. Said target analytes may be collected following epitachophoresis and used for desired downstream applications and further analysis.

8. 发明申请

US20220251645A1 NUCLEIC ACID SEQUENCING USING NANOTRANSISTORS 有权
公开(公告)号：US20220251645A1
公开(公告)日：2022-08-11
申请号：US17731818
申请日：2022-04-28
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER
IPC分类号： C12Q1/6869 , C12Q1/6823
摘要： Embodiments may include a nucleic acid molecule system. The system may include a nucleic acid polymerase attached to a tether compound. The polymerase may be configured to elongate a nascent strand. The system may also include a nucleotide attached to a label compound. The label compound may include a moiety. The system may further include a transistor in electrical communication with a power supply. The polymer may be attached to the transistor. In addition, the system may include a meter device configured to measure an electrical characteristic of the transistor from the moiety after the label compound is cleaved from the nucleotide by the nucleic acid polymerase.

9. 发明申请

US20220018809A1 TUNNEL JUNCTIONS IN MICROFLUIDIC ARRAYS FOR MOLECULAR RECOGNITION 有权
公开(公告)号：US20220018809A1
公开(公告)日：2022-01-20
申请号：US17490479
申请日：2021-09-30
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER , Juraj TOPOLANCIK
IPC分类号： G01N27/447 , G01N27/327 , G01N33/487 , B01L3/00 , H01L43/02 , H01L43/10 , H01L43/12
摘要： Embodiments of the present technology may allow for the analysis of molecules by tunneling recognition at a tunneling junction. A tunneling junction of the present technology can include an insulating layer between two electrodes. A voltage may be applied to the electrodes. When a molecule makes contact with both electrodes, the molecule allows current to tunnel through the molecule. The characteristics of the current may aid in identifying a portion of the molecule, for example, a particular nucleotide or base present in a nucleic acid molecule. Methods and systems for analysis of molecules are described.

10. 发明申请

US20200158687A1 TUNNEL JUNCTIONS IN MICROFLUIDIC ARRAYS FOR MOLECULAR RECOGNITION 审中-公开
公开(公告)号：US20200158687A1
公开(公告)日：2020-05-21
申请号：US16750574
申请日：2020-01-23
申请人： Roche Sequencing Solutions, Inc.
发明人： Yann ASTIER , Juraj TOPOLANCIK
IPC分类号： G01N27/447 , H01L43/12 , H01L43/10 , H01L43/02 , B01L3/00 , G01N33/487 , G01N27/327
摘要： Embodiments of the present technology may allow for the analysis of molecules by tunneling recognition at a tunneling junction. A tunneling junction of the present technology can include an insulating layer between two electrodes. A voltage may be applied to the electrodes. When a molecule makes contact with both electrodes, the molecule allows current to tunnel through the molecule. The characteristics of the current may aid in identifying a portion of the molecule, for example, a particular nucleotide or base present in a nucleic acid molecule. Methods and systems for analysis of molecules are described.

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